Pediatric Fibrodysplasia Ossificans Progressiva (Myositis Ossificans) Differential Diagnoses

Updated: Aug 14, 2018
  • Author: Robert J Pignolo, MD, PhD; Chief Editor: Lawrence K Jung, MD  more...
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Diagnostic Considerations

Fibrodysplasia ossificans progressiva (FOP) must be distinguished from other genetic conditions of heterotopic ossification (HO), as well as from nonhereditary heterotopic ossification (NHHO).

  • Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive ectopic ossification. [12]

    • POH is clinically defined by cutaneous ossification that characteristically presents during childhood and progresses to involve subcutaneous and deep connective tissues, including muscle and fascia, in the absence of multiple features of Albright hereditary osteodystrophy (AHO) or hormone resistance.

    • Fibrodysplasia ossificans progressiva is distinguished from POH by the lack of cutaneous ossification, the presence of congenital malformation of the great toes, and preosseous tumorlike inflammation or “flare-ups.”

    • POH is one of numerous related genetic disorders, including AHO, pseudohypoparathyroidism (PHP), and osteoma cutis (OC), which share the common features of superficial ossification and association with inactivating mutations of GNAS, the gene that encodes the alpha subunit of the G-stimulatory protein of adenylyl cyclase.

  • NHHO follows trauma or other injury in most cases. [13] It can be observed at any age but is rare in children younger than 10 years. In children and young adults, sites of extraskeletal ossification tend to be periarticular or at the sites of blunt trauma or localized injury. NHHO presents as a painful soft tissue mass, which can be easily confused with malignant lesions such as osteosarcoma and soft tissue sarcoma. [14] Diagnosis of this condition may be difficult and requires radiological or histological findings after genetic conditions of heterotopic ossification have been excluded.

  • Fibrodysplasia ossificans progressiva is commonly misdiagnosed as aggressive juvenile fibromatosis, lymphedema, or soft tissue sarcoma. [15] The misdiagnosis of fibrodysplasia ossificans progressiva approaches 90% in individuals with fibrodysplasia ossificans progressiva worldwide. The correct diagnosis of fibrodysplasia ossificans progressiva can be made clinically, even before radiographic evidence of heterotopic ossification is seen, if soft tissues lesions are associated with symmetrical malformations of the great toes. Children often undergo unnecessary and harmful diagnostic biopsies that exacerbate the progression of the condition. This can be particularly dangerous at any anatomic site but especially so in the neck, back, or jaw where asymmetric heterotopic ossification can lead to rapidly progressive spinal deformity, exacerbation of thoracic insufficiency syndrome, or rapid ankylosis of the temporomandibular joints.

  • Other possibilities to consider include lymphoma, desmoids tumors, isolated congenital malformations, brachydactyly (isolated), and juvenile bunions.

Differential Diagnoses